Gender comparisons in human lung cancer: analysis of p53 mutations, anti-p53 serum antibodies and C-erbB-2 expression

Abstract

Little is known about the molecular mechanisms of lung carcinogenesis in women. We initiated an investigation of the role of gender in pulmonary carcinogenesis by analysis of p53 mutations, immunohistochemistry, serum antibodies and c-erbB-2 expression in a series of 63 male and 44 female lung cancer patients whose tumors were resected at the Mayo Clinic between 1991 and 1992. There were 102 smokers and 5 never smoked. Adenocarcinoma was the more frequent histological type in women (62%) than in men (41%). Sequence analysis of exons 5-8 in 42 females and 49 males identified 44 p53 mutations in 42 tumors (46%). Base substitution mutations showed a preponderance of G:C-->T:A transversions, which were more frequent in women than men (40 versus 25%) and in individuals exposed to asbestos. c-erbB-2 immunohistochemical staining was identified more frequently in females (nine cases) than males (two cases). Marked immunohistochemical staining for p53 positively correlated with the presence of missense mutations in exons 5-8 (81%, P < 0.001). Seven missense mutations (four in exon 5, two in exon 6, one in exon 8) were identified in five of nine patients who had serum antibodies recognizing p53; tumors from these patients were also strongly positive for p53 by immunohistochemistry. These and other results indicate gender differences in the genetic and biochemical alterations in lung cancer and generate hypothesis regarding gender differences in lung cancer susceptibility.

TP53 Mutation Spectrum in Lung Cancer Is Not Different in Women and Men

“…10). Consistent with these results, in previous studies that reported a higher frequency of G:C-to-T:A mutations in women, gender differences were not statistically significant (8,5). Women smoked fewer cigarettes than men in these studies.…”

“…Differences in type of mutations in TP53 were estimated by Fisher's exact tests when expected counts were V5, or m 2 tests. Using two-sided tests, a of 0.05, and the frequency of G:C-to-T:A mutations in TP53 in previous studies of 25% or 27% in men and 40% in women, our study had 89% or 78% power to detect a statistical difference (8,5). Differences in pack-years of smoking were compared using t-tests.…”

EGFR exon 19 in‐frame deletion and polymorphisms of DNA repair genes in never‐smoking female lung adenocarcinoma patients

“…Sex-specific differences have also been observed for associations between EGFR mutations and the HLA-A2(þ) allele. 24 In addition, p53 transversion mutations 25 and insertion/deletion mutations 26 are more frequent in females. Various carcinogens originated from environmental exposures or endogenous processes constantly threaten DNA integrity.…”

Human variability and susceptibility to trichloroethylene.

“…Several epidemiological studies of cigarette smoke have shown that, at the same exposure level, women differ in their resistance to lung damage compared to men. Xu et al (94) report that adverse effects of smoking on pulmonary function are greater in women than in men, and other studies indicate sex differences in lung dysfunction, and in genetic and biochemical alterations in lung cancer (95)(96)(97).…”